Cardiovascular and respiratory effects of medetomidine in dogs and influence of anticholinergics

A total of 10 laboratory beagles was used to determine the cardiovascular and respiratory effects of medetomidine. The effects of atropine sulphate and glycopyrrolate on heart rate were also observed. Xylazine was included as a positive control. Medetomidine induced initial hypertension followed by a longer lasting hypotensive period. Evident bradycardia with second degree atrioventricular blocks and decrease in respiratory frequency was observed. Atropine sulphate and glycopyrrolate transiently abolished the bradycardic effect of medetomidine. Xylazine exhibited a similar cardiovascular and respiratory pattern to medetomidine.     

Total intravenous anaesthesia with propofol or propofol/ketamine in spontaneously breathing dogs premedicated with medetomidine

The cardiorespiratory parameters, the depth of anaesthesia and the quality of recovery were evaluated in six spontaneously breathing dogs that had been premedicated with medetomidine (40 microg/kg, supplemented with 20 microg/kg an hour later), administered with either propofol (1 mg/kg followed by 0.15 mg/kg/minute, intravenously), or with ketamine (1 mg/kg followed by 2 mg/kg/hour, intravenously) and propofol (0.5 mg/kg followed by 0.075 mg/kg/minute, intravenously). The dogs' heart rate and mean arterial blood pressure were higher and their minute volume of respiration and temperature were lower when they were anaesthetised with propofol plus ketamine, and a progressive hypercapnia leading to respiratory acidosis was more pronounced. When the dogs were anaesthetised with propofol/ketamine they recovered more quickly, but suffered some unwanted side effects. When the dogs were anaesthetised with propofol alone they recovered more slowly but uneventfully.     

Effects of medetomidine premedication on propofol infusion anaesthesia in dogs

Observations of cardiovascular and respiratory parameters were made on six dogs anaesthetized on two separate occasions for 120 minutes with a propofol infusion, once without premedication and once following premedication with 10 μg kg-¹ of intramuscular medetomidine. During anaesthesia the heart rate and cardiac index tended to be lower following medetomidine premedication, while the mean arterial pressure was significantly greater (p<0.05). Although the differences were not statistically significant, the systemic vascular resistance, pulmonary vascular resistance and stroke volume index were also greater in dogs given medetomidine. The mean arterial oxygen and carbon dioxide tensions were similar under both regimens, but in 2 dogs supplementary oxygen had to be administered during anaesthesia to alleviate severe hypoxaemia on both occasions they were anaesthetized. Minute and tidal volumes of respiration tended to be greater in dogs not given medetomidine but medetomidine premedication appeared to have no effect on venous admixture. Dogs given medetomidine received intramuscular atipamezole at the end of the 120 min. propofol infusion; the mean time from induction of anaesthesia to walking without ataxia was 174. min in the unpremedicated dogs and 160 min. in the dogs given atipamezole. The mean blood propofol concentration at which the dogs walked without ataxia was higher in the unpremedicated animals (2.12 ± 0.077 μg. ml-¹ compared with 1.27 ± 0.518 μg. ml-¹ in the premedicated dogs). The oxygen delivery to the tissues was lower after medetomidine premedication (p = 0.03) and the oxygen consumption was generally lower after medetomidine premedication but the difference did not achieve statistical significance. No correlation could be demonstrated between blood propofol concentration and cardiac index, systemic or pulmonary vascular resistance indices, systolic, diastolic or mean arterial blood pressures.     

Sedative and analgesic effects of medetomidine in dogs

The sedative and analgesic effects of medetomidine were studied in 18 laboratory beagles in a randomized cross-over study which was carried out in a double-blind fashion. Xylazine was included as a positive control and placebo as a negative control. Medetomidine was used at doses of 10, 30, 90 and 180 micrograms/kg i.m. compared to a dose of 2.2 mg/kg xylazine i.m. Parameters closely related to sedation were used to measure the degree of sedation. These were a posture variable (including evaluation of the dog's posture without external disturbance and resistance when laid recumbent) and a relaxation variable (including relaxation of the jaws, upper eyelids and anal sphincter). The first signs of sedation were recorded 1.5-3.5 min after administration of both drugs. The dogs sat down at 0.6-2.6 min post-injection and became prone at 1.9-5.9 min. Medetomidine dose-dependently affected the posture of the dogs and the relaxation variable--the higher the dose, the stronger and longer lasting the effect recorded. The sedative effect of xylazine was comparable to a medetomidine dose of 30 micrograms/kg. The analgesic effect was assessed as changes in the response to superficial pain induced by electrical stimuli. The response threshold increased significantly with both drugs and the effect of medetomidine was dose-dependent. The effects of the doses of 30 micrograms/kg medetomidine and 2.2 mg/kg xylazine did not differ significantly. In summary, medetomidine possessed an excellent sedative effect associated with analgesia in dogs.     

Effect of medetomidine on breathing and inspiratory neuromuscular drive in conscious dogs

OBJECTIVE: To evaluate the effects of the alpha2-adrenoceptor agonist medetomidine on respiratory rate (RR), tidal volume (V(T)), minute volume (V(M)), and central respiratory neuromuscular drive as determined by inspiratory occlusion pressure (IOP) during increasing fractional inspired concentrations of carbon dioxide (FiCO2) in conscious dogs. ANIMALS: 6 healthy dogs (3 males and 3 females). PROCEDURE: Dogs were administered 0, 5, or 10 microg of medetomidine/kg i.v. We measured RR, V(T), V(M), and IOP for the first 0.1 second of airway occlusion (IOP0.1) during FiCO2 values of 0%, 2.5%, 5.0%, and 75% at 15 minutes before and 5, 30, and 60 minutes after administration of medetomidine. RESULTS: Increases in FiCO2 significantly increased RR, V(T), and V(M). The i.v. administration of 5 and 10 microg of medetomidine/kg significantly decreased RR and V(M) at 5, 30, and 60 minutes for FiCO2 values of 2.5% and 5.0% and at 30 and 60 minutes for an FiCO2 value of 75%. The IOP0.1 was decreased after 30 minutes only for an FiCO2 value of 7.5% in dogs administered 5 and 10 microg of medetomidine/kg. The IOP0.1 was decreased at 60 minutes after administration of 10 microg of medetomidine/kg for an FiCO2 value of 7.5%. CONCLUSIONS AND CLINICAL RELEVANCE: The i.v. administration of medetomidine decreases RR, V(M), and central respiratory drive in conscious dogs. Medetomidine should be used cautiously and with careful monitoring in dogs with CNS depression or respiratory compromise.     

Hemodynamic effects of an intravenous infusion of medetomidine at six different dose regimens in isoflurane-anesthetized dogs

This study investigated the dose dependency of the hemodynamic effects of IV medetomidine (MED) constant-rate infusion (CRI) during isoflurane anesthesia. Twenty-four healthy beagles randomly received one of six MED CRI regimens. A loading dose of MED was administered IV at 0.2, 0.5, 1.0, 1.7, 4.0, or 12.0 ug/kg-1 for 10 minutes, followed by a maintenance CRI providing identical dose amounts over 60 minutes. Heart rate and mean arterial blood pressure were recorded, blood gases were analyzed, and cardiac index (CI) was determined. Statistical analysis involved a repeated measures linear model. Baseline CI demonstrated a dose-dependent decrease as the MED dose increased, with decreases of 14.9% (SD, 12.7%), 21.7% (17.9%), 27.1% (13.2%), 44.2% (9.7%), 47.9% (8.1%), and 61.2% (14.1%) at doses of 0.2, 0.5, 1.0, 1.7, 4.0, and 12.0 ug/kg-1, respectively. The four lowest doses induced limited and transient changes in heart rate, mean arterial pressure, and CI. Further investigation into potential perioperative uses of MED CRI is warranted.     

Non-invasive measurement of the cardiovascular effects of chronic hypoxaemia on dogs living at moderately high altitude

Pulmonary hypertension is a well-recognised condition in dogs, and, among other mechanisms, is caused by hypoxia. In order to evaluate the effect of chronic hypobaric hypoxia on pulmonary arterial pressure in dogs, a colony of 19 clinically and biochemically healthy Greenland sled dogs living permanently at at least 2300 m above sea level (altitude dogs) and 10 clinically healthy Greenland sled dogs living at 700 to 900 m above sea level (control dogs) were examined. Investigations were made of the dogs' packed-cell volume, venous and arterial blood gases, electrocardiogram, blood pressure and echocardiograph, including the calculation of pulmonary arterial pressure by Doppler examination of tricuspid regurgitation. The altitude dogs had a marked arterial hypoxaemia with a mean (sd) oxygen partial pressure of 61.9 (7.4) mmHg and a significantly lower arterial oxygen saturation (90.7 [3.7] per cent) than the control dogs (96.7 [0.8] per cent). In eight of the altitude dogs, tricuspid regurgitation allowed calculation of the systolic pulmonary arterial pressure, which was 29.5 (10.4) mmHg. Eight of the control dogs had tricuspid insufficiency, and their derived systolic pulmonary arterial pressure was significantly lower (17.4 [3.9] mmHg).     

Comparative cardiovascular, analgesic, and sedative effects of medetomidine, medetomidine-hydromorphone, and medetomidine-butorphanol in dogs

OBJECTIVE: To compare sedative, analgesic, and cardiopulmonary effects after IV administration of medetomidine (20 microg/kg), medetomidine-hydromorphone (20 microg of medetomidine/kg and 0.1 mg of hydromorphone/kg), and medetomidine-butorphanol (20 microg of medetomidine/kg and 0.2 mg of butorphanol tartrate/kg) in dogs. ANIMALS: 6 dogs healthy mixed-breed dogs. PROCEDURE: Instruments were surgically inserted, and heart rate (HR), respiratory rate (RR), systolic arterial pressure (SAP), mean arterial pressure (MAP), diastolic arterial pressure (DAP), mean pulmonary arterial pressure (MPAP), pulmonary capillary wedge pressure (PCWP), central venous pressure (CVP), core body temperature, and cardiac output (CO) were measured 0, 5, 10, 15, 30, 45, and 60 minutes after injection. Cardiac index (CI), stroke volume (SV), stroke index (SI), systemic vascular resistance (SVR), and pulmonary vascular resistance (PVR) were calculated. Arterial samples for blood gas analysis were collected 0, 15, and 45 minutes after injection. Intensity of analgesia, degree of sedation, and degree of muscle relaxation were evaluated at aforementioned time points and 75, 90, 120, 150, 180, and 210 minutes after injection. RESULTS: Administration of medetomidine, medetomidine-hydromorphone, and medetomidine-butorphanol was associated with increases in SAP, MAP, DAP, MPAP, PCWP, CVP, SVR, PVR, core body temperature, and PaCO2 and decreases in HR, CO, CI, SV, SI, RR, pH, and PaO2. Clinically important differences were not detected among treatments. Medetomidine-hydromorphone and medetomidine-butorphanol provided a longer duration of sedation and better quality of analgesia, compared with medetomidine alone. CONCLUSIONS AND CLINICAL RELEVANCE: Medetomidine-hydromorphone or medetomidine-butorphanol is associated with improved analgesia and sedation but has cardiopulmonary effects comparable to those for medetomidine alone.     

Comparison of diazepam–ketamine and thiopentone for induction of anaesthesia in healthy dogs

Objective To compare the anaesthetic and cardiopulmonary effects of a diazepam–ketamine combination with thiopentone for induction of anaesthesia in dogs. Animal population Twenty healthy dogs of various breeds weighing between 3.8 and 42.6 kg undergoing major orthopaedic or soft tissue surgery. Materials and methods Pre‐anaesthetic medication in all cases was intramuscular acepromazine and methadone given 30 minutes before induction of anaesthesia. Each animal was then randomly assigned to receive either thiopentone or diazepam and ketamine. Quality of conditions for, and time to tracheal intubation were recorded. Anaesthesia was maintained with halothane in oxygen and nitrous oxide. Heart rate, respiratory rate, systolic blood pressure, end tidal carbon dioxide tensions and oxygen saturation were recorded at 10 minute intervals throughout surgery. The quality of recovery from anaesthesia was assessed. Results The quality of induction in both groups was satisfactory. The total mean time (± SD) to tracheal intubation (162 ± 84 seconds) was significantly longer in dogs receiving diazepam and ketamine compared to dogs receiving thiopentone (62 ± 28 seconds). Heart rate, systolic blood pressure and end tidal carbon dioxide concentration were not significantly different between groups. Respiratory rate was significantly higher in the diazepam–ketamine group between 0 and 30 minutes. The quality of recovery was similar in each group. Conclusions There appear to be fewer differences between the induction agents examined in this study than was previously believed. No pressor, or other cardiovascular stimulating effects were detected in the dogs that received diazepam and ketamine. Clinical relevance The absence of obvious differences between groups suggests that pre‐anaesthetic medication, inhaled anaesthetics and the physiological effects of surgery itself probably had a greater effect on the variables studied than the induction agent used. Further studies are required to determine whether diazepam and ketamine offers significant advantages over other induction agents in the unhealthy dog.     

A comparative study of medetomidine/ketamine and xylazine/ketamine anaesthesia in dogs

The anaesthetic and physiological effects of a combination of 40 micrograms medetomidine with 2.5 ketamine, 5.0 or 7.5 mg/kg administered intramuscularly were compared with the effects of a combination of 1 mg/kg xylazine and 15 mg/kg ketamine. All the combinations rapidly induced an anaesthetic state that permitted endotracheal intubation, with the absence of the pedal reflex and with good muscle relaxation, and induced bradycardia that was less pronounced as the dose of ketamine was increased. All the combinations produced a decrease in respiratory rate. Increasing the dose of ketamine combined with medetomidine resulted in a very significant prolongation of the duration of anaesthesia, the duration of muscle relaxation and the arousal time. The duration of the anaesthetic effects of 40 micrograms/kg medetomidine with 5 mg/kg ketamine was comparable to that provided by the recommended xylazine/ketamine combination but the period of muscle relaxation was significantly longer. The recovery from medetomidine/ketamine took longer than recovery from xylazine/ketamine but there were fewer side effects.     

Clinical, cardiovascular and respiratory effects of R8110 in premedicated dogs

The clinical, cardiovascular and respiratory effects after i.v. administration of R8110, a fluoro analogue of etomidate (Fig. 1), were studied in pre-medicated dogs. The clinical observations were made at doses of 3 and 4 mg/kg body weight (BW) injected slowly i.v., whereas cardiovascular and respiratory studies were carried out at a dose rate of 3 mg/kg R8110 i.v. Induction and recovery were smooth and no significant side-effects were observed. The cardiovascular system was slightly influenced, but respiration was hardly affected. The effect of pre-medication on respiration and the cardiovascular system was hardly potentiated by R8110. Although there were significant changes in cardiovascular and biochemical parameters, all values remained within physiological limits. R8110 appeared to be a safe and reliable induction agent.     

The effects of medetomidine hydrochloride on the electroretinogram of normal dogs

Purpose  To determine the effects of a standardized intravenous dose of an α-2 agonist (Domitor^®, Orion Pharma, distributed by Pfizer Animal Health, Exton, PA) on the electroretinogram (ERG) response in normal dogs.
Methods  Twenty-five normal dogs were used to collect ERG responses including a- and b-wave implicit times (IT) and amplitudes (AMP) before and after administration of medetomidine. Dogs were dark adapted for 20 min and ERGs were obtained using the HMsERG (RetVetCorp Inc., Columbia, MO). The QuickRetCheck protocol (Narfström) was employed to provide the following flash intensities: 10 mcd s/m², 3 cd s/m², and 10 cd s/m². ERGs were repeated after 375 µg/m² of medetomidine intravenously. Statistical analysis of the difference between the responses before and after medetomidine at all flash intensities was performed using a mixed effects model for anova .
Results  The P value for the effect of medetomidine on each of the ERG responses was < 0.01. The estimates of the effect of medetomidine were (+)1.35 ms, (–)23 µV, (+)3.16 ms, and (–)47 µV for the a-wave IT, a-wave AMP, b-wave IT, and the b-wave AMP, respectively.
Conclusions  Medetomidine significantly prolongs the implicit time and lowers the amplitude response of both the a- and b-waves in normal dogs at all flash intensities examined. Clinically, however, medetomidine only minimally affects the retinal responses and is a viable choice for use in dog ERGs.     

The effects of medetomidine on radial nerve blockade with mepivacaine in dogs

OBJECTIVE: To compare the sensory and motor effects of adding medetomidine to mepivicaine, administered either perineurally or systemically, for radial nerve block in dogs. STUDY DESIGN: Prospective randomized cross-over study. ANIMALS: Six healthy Beagles, aged 18.7 +/- 6.3 months and weighing 10.4 +/- 1.3 kg. METHODS: Dogs were anesthetized briefly with sevoflurane on three separate occasions and received each treatment administered in random order: mepivacaine 5 mg kg(-1) perineurally around the radial nerve with saline 0.01 mL kg(-1) intramuscularly (CONTROL); mepivacaine 5 mg kg(-1) and medetomidine 0.01 mg kg(-1) combined, perineurally with saline 0.01 mL kg(-1) intramuscularly (MEDPN); mepivacaine 5 mg kg(-1) perineurally around the radial nerve with medetomidine 0.01 mg kg(-1) intramuscularly (MEDIM). All nerve blocks were performed with the aid of a nerve locator. Motor effects were evaluated based on the ability to bear weight. Sensory effects were evaluated by the response to a graded-electrical stimulus. These were evaluated at 5-minute intervals for the first hour, and at 10-minute intervals thereafter. Mean intervals were calculated as follows: time to motor block onset, duration of motor block, time to peak sensory block, duration of peak sensory block (i.e. period of no response to maximal stimulus intensity), and duration of residual sensory block (i.e. time to return to baseline sensory function). Treatment means were compared using a one-way analysis of variance for repeated measures and, where significant differences were noted, a Student-Newman-Keuls test was applied; p < 0.05 was considered significant. RESULTS: Medetomidine, administered either systemically or perineurally, significantly prolonged duration of peak motor block, peak sensory block, and residual sensory block compared with CONTROL. CONCLUSION: Medetomidine prolonged sensory and motor blockade after radial nerve block with mepivacaine in dogs. CLINICAL RELEVANCE: Medetomidine may prove to be a useful adjunct to peripheral nerve blockade with local anesthetics.     

Echocardiographic evaluation of the effects of medetomidine and xylazine in dogs

The echocardiographic effects of medetomidine and xylazine were evaluated in 6 healthy dogs. Values for echocardiographic variables were significantly different from pre-treatment values after administration of both drugs. The effects of medetomidine were similar to that of xylazine. Because of their cardiac depressant effects, both drugs should be used with care in sick dogs.     

Clinical effects and pharmacokinetics of medetomidine and its enantiomers in dogs

The clinical effects and pharmacokinetics of medetomidine (MED) and its enanti-omers, dexmedetomidine (DEX) and levomedetomidine (LEVO) were compared in a group of six beagle dogs. The dogs received intravenously (i.v.) a bolus of MED (40 microg/kg), DEX (20 and 10 microg/kg), LEVO (20 and 10 microg/kg), and saline placebo in a blinded, randomized block study in six separate sessions. Sedation and analgesia were scored subjectively, and the dogs were monitored for heart rate, ECG lead II, direct blood pressure, respiratory rate, arterial blood gases, and rectal body temperature. Blood samples for drug analysis were taken. Peak sedative and analgesic effects were observed at mean (+/- SD) plasma levels of 18.5 +/- 4.7 ng/mL for MED40, 14.0 +/- 4.5 ng/mL for DEX20, and 5.5 +/- 1.3 ng/mL for DEX10. The overall level of sedation and cardiorespiratory effects did not differ between MED40, DEX20 and DEX10 during the first hour, apparently due to a ceiling effect. However, the analgesic effect of DEX20 lasted longer than the effect of the corresponding dose of racemic medetomidine, suggesting greater potency for dexmedetomidine in dogs. Levomedetomidine had no effect on cardio-vascular parameters and caused no apparent sedation or analgesia. The pharmacokinetics of dexmedetomidine and racemic medetomidine were similar, but clearance of levomedetomidine was more rapid (4.07 +/- 0.69 L/h/kg for LEVO20 and 3.52 +/- 1.03 for LEVO10) than of the other drugs (1.26 +/- 0.44 L/h/kg for MED40, 1.24 +/- 0.48 for DEX20, and 0.97 +/- 0.33 for DEX10).     

The sedative effects of low-dose medetomidine and butorphanol alone and in combination intravenously in dogs

ObjectiveTo evaluate the sedative effects of intravenous (IV) medetomidine (1 μg kg^?1) and butorphanol (0.1 mg kg^?1) alone and in combination in dogs.Study designProspective, blinded, randomized clinical trial.AnimalsSixty healthy (American Society of Anesthesiologists I) dogs, aged 6.2 ± 3.2 years and body mass 26 ± 12.5 kg.MethodsDogs were assigned to four groups: Group S (sodium chloride 0.9% IV), Group B (butorphanol IV), Group M (medetomidine IV) and Group MB (medetomidine and butorphanol IV). The same clinician assessed sedation before and 12 minutes after administration using a numerical scoring system in which 19 represented maximum sedation. Heart rate (HR), respiratory rate, pulse quality, capillary refill time and rectal temperature were recorded after each sedation score assessment. Sedation scores, sedation score difference (score after minus score before administration) and patient variables were compared using one-way anova for normally distributed variables and Kruskal–Wallis test for variables with skewed distributions and/or unequal variances. Where significance was found, further evaluation used Bonferroni multiple comparisons for pair-wise testing.ResultsBreed, sex, neuter status, age and body mass did not differ between groups. Sedation scores before substance administration were similar between groups (p = 0.2). Sedation scores after sedation were significantly higher in Group MB (mean 9.5 ± SD 5.5) than in group S (2.5 ± 1.8) (p < 0.001), group M (3.1 ± 2.5) (p < 0.001) and group B (3.7 ± 2.0) (p = 0.003). Sedation score difference was significantly higher in Group MB [7 (0–13)] than in Group S [0 (?1 to 4)] (p < 0.001) and Group M [0 (0–6)] (p < 0.001). HR decreased significantly in Groups M and MB compared with Group S (p < 0.05).Conclusion and clinical relevanceLow-dose medetomidine 1 μg kg^?1 IV combined with butorphanol 0.1 mg kg^?1 IV produced more sedation than medetomidine or butorphanol alone. HR was significantly decreased in both medetomidine groups.     

Comparison of disposable circle and 'to-and-fro' breathing systems during anaesthesia in dogs

Low-flow anaesthesia is beneficial in terms of reducing atmospheric pollution with waste anaesthetics and improving economy. This study compared a disposable circle and a 'to-and-fro' breathing system at low fresh gas flows (10 ml/kg/minute) in 19 dogs undergoing ovariohysterectomy. Ten dogs were assigned to the circle and nine to the to-and-fro breathing system. Fractional inspired halothane, end-tidal carbon dioxide and halothane were higher and mean blood pressure was lower in dogs using the to-and-fro system, possibly indicating an increased anaesthetic depth in this group. Use of both systems resulted in an elevated inspired carbon dioxide level, although this was significantly lower in the circle system. Further work will be required to determine the clinical relevance of this difference and whether rebreathing can be eliminated by higher fresh gas flows. The disposable circle studied may be used safely in dogs.     

Dose-sparing effects of romifidine premedication for thiopentone and halothane anaesthesia in the dog

Two intravenous doses of romifldine (40 and 80 μg/kg) and a placebo were compared as premedicants for anaesthesia induced with thiopentone and maintained using halothane in oxygen. Romifldine significantly and linearly reduced the induction dose of thiopentone; placebo-treated dogs required 15.1 ± 3.6 mg/kg, while dogs treated with 40 μg/kg and 80 μg/kg romifldine required 6.5 ± 1.6 and 3.9 ± 0.3 mg/kg thiopentone, respectively.
Romlfldine also significantly and linearly reduced the end tidal halothane concentration necessary to maintain a predetermined level of anaesthesia; piacebetreated dogs required 1.6 ± 0.3 per cent halothane, while dogs treated with 40 μg/kg and 80 μg/kg romifldine required 1.3 ± 0.4 and 0–8 ± 0.2 per cent, respectively.
Romifldine produced a significant shortening In the recovery from anaesthesia, and the higher dose of romlfldine significantly improved the overall quality of anaesthesia.